IMMUNOLOGY & SEROLOGY (TopnotcherQT) > HUMAN IMMUNODEFICIENCY VIRUS > Flashcards
HUMAN IMMUNODEFICIENCY VIRUS Flashcards
Types of HIV:
- HIV-1 - more pathogenic stain
- HIV-2 - less pathogenic, lower transmission rate
Former names of HIV-1:
- HTLV-III
- Lymphadenopathy-associated virus (LAV)
- AIDS-associated retrovirus (ARV)
HIV-1 groups:
- Group M (the main or major group)
- Group N (the non-M/ non-O, or New group)
- Group O (the outlier group)
How many subtypes does HIV-1 Group M have?
9 subtypes
- A
- B
- C
- D
- F, G, H, J, and K
Most predominant subtype in the US and Europe
Subtype B
Most predominant subtype worldwide
Subtype C
Encoded by the ENV gene (envelope gene); serves for attachment of HIV to CD4 cells:
Gp41/Gp120 complex
The protein that traverses the membrane:
Gp41
A knoblike structure attached to Gp41:
Gp120
Nucleocapsid core protein of the virus; encoded by the gag gene (group antigen)
p24
Matrix shell protein; encoded by the gag gene 9group antigen)
p17
Transcribes viral RNA to DNA:
Reverse transcriptase
Reverse transcriptase is encoded by ____ gene
pol gene (polymerase gene)
Standard screening test for HIV antibody:
ELISA (Enzyme-Link Immunosorbent Assay)
Confirmatory test for HIV:
Western Blot ASsay
Western Blot Assay detects _____ Abs specific to _____
Western Blot Assay detects IgG Abs specific to HIV antigens
In Western Blot Assay, the separated HIV-1 proteins are transferred to a _______.
nitrocellulose membrane
CDC CRITERIA FOR POSITIVE INTERPRETATION OF WESTERN BLOT TEST:
Presence of at least 2 out of 3 bands to:
- p24
- Gp41
- Gp120/160
What is the earliest HIV serological marker to appear?
p24
note: High in initial weeks of infection during the early burst of viral replication, then become undetectable as antibody to p24 develops appears about 1 week before the appearance of HIV antibody during the acute stage of infection, allowing for slightly earlier detection of the virus.
All of the following describe HIV except
a. it possesses an outer envelope.
b. it contains an inner core with p24 antigen.
c. it contains DNA as its nucleic acid.
d. it is a member of the retrovirus family
c. it contains DNA as its nucleic acid.
HIV characteristics:
1. Outer envelope (a): Correct, derived from host cell membrane.
2. Inner core with p24 antigen (b): Correct, core protein.
3. Member of retrovirus family (d): Correct, utilizes reverse transcription.
However, HIV’s genetic material consists of:
- Single-stranded RNA (+) sense
Not DNA. Reverse transcriptase converts RNA to double-stranded DNA during replication.
HIV virions bind to host T cells through which receptors?
a. CD4 and CD8
b. CD4 and the IL-2 receptor
c. CD4 and CCR5
d. CD8 and CCR2
c. CD4 and CCR5.
HIV-1 virions bind to host T cells via:
Primary Receptor
1. CD4 (cluster of differentiation 4): Primary receptor, essential for viral attachment.
Co-Receptors
1. CCR5 (CC chemokine receptor 5): Primary co-receptor, facilitating viral entry.
2. CXCR4: Alternate co-receptor, utilized by some HIV-1 strains.
CD4+ T cells (helper T cells) are primary targets.
Suppose a combination immunoassay to screen for HIV infection was positive, but the confirmatory test was negative. Which of the following tests should be performed?
a. p24 antibody
b. Western blot
c. PCR for HIV-1 RNA
d. No further testing is needed, and the screening test should be interpreted as a false positive.
d. No further testing is needed, and the screening test should be interpreted as a false positive.
When:
1. Combination immunoassay (screening) is positive.
2. Confirmatory test (e.g., Western blot) is negative.
Guidelines recommend:
1. No further testing.
2. Interpret screening result as false positive.
Exceptions:
1. Recent exposure (<3 months).
2. Immunocompromised individuals.
3. Clinical suspicion.
In these cases, repeat testing or PCR may be considered.
Which of the following is typical of the latent stage of HIV infection?
a. Proviral DNA is attached to cellular DNA.
b. Large numbers of viral particles are synthesized.
c. A large amount of viral RNA is synthesized.
d. Viral particles with no envelope are produced.
a. Proviral DNA is attached to cellular DNA.
Characteristics of HIV latent stage:
Key Features
- Proviral DNA integration: HIV genetic material combines with host cell DNA.
- Low or undetectable viral replication.
- Minimal viral transcription.
- No active viral production.
- Immune system evasion.
Latency Sites
1. Resting memory CD4+ T cells.
2. Macrophages.
3. Dendritic cells.
Other Options
1. b & c: High viral replication occurs during acute infection, not latency.
2. d: Viral particles require an envelope for infectivity.
The decrease in T-cell numbers in HIV-infected individuals is caused by
a. lysis of host T cells by replicating virus.
b. fusion of the T cells to form syncytia.
c. killing of the T cells by HIV-specific cytotoxic T cells.
d. all of the above.
d. all of the above.
Explanation
The decrease in T-cell numbers in HIV-infected individuals is multifactorial:
- Lysis of host T cells by replicating virus (a): HIV replication causes direct cellular damage.
- Fusion of T cells to form syncytia (b): HIV-infected cells fuse, leading to giant cells and subsequent cell death.
- Killing of T cells by HIV-specific cytotoxic T cells (c): Immune response against infected cells.
Additional mechanisms:
- Apoptosis (programmed cell death)
- Immune exhaustion
- Dysfunction of immune cells
- Destruction of lymphoid tissues
The most common means of HIV transmission worldwide is through
a. blood transfusions.
b. intimate sexual contact.
c. sharing of needles in intravenous drug use.
d. transplacental passage of the virus.
b. intimate sexual contact.
According to UNAIDS and the World Health Organization (WHO), the primary modes of HIV transmission globally are:
Sexual Transmission (approx. 80-85%)
1. Heterosexual contact (majority)
2. Homosexual contact
Other Modes
1. Sharing needles/syringes (injectable drug use): 5-10%
2. Mother-to-child transmission (transplacental, breastfeeding): 5-7%
3. Blood transfusions: rare (due to screening)
4. Occupational exposure (healthcare workers): rare
The drug zidovudine is an example of a
a. nucleoside analogue reverse-transcriptase inhibitor.
b. nonnucleoside reverse-transcriptase inhibitor.
c. protease inhibitor.
d. fusion inhibitor.
a. nucleoside analogue reverse-transcriptase inhibitor (NRTI).
Zidovudine (AZT) works by:
Mechanism
1. Mimicking natural nucleosides.
2. Inhibiting HIV’s reverse transcriptase enzyme.
3. Blocking viral RNA conversion to DNA.
Classifications
1. NRTIs (e.g., zidovudine, lamivudine).
2. Non-NRTIs (e.g., nevirapine, efavirenz).
3. Protease inhibitors (e.g., lopinavir, ritonavir).
4. Fusion inhibitors (e.g., enfuvirtide).
Clinical Use
Zidovudine:
1. Treats HIV-1 infection.
2. Prevents mother-to-child transmission.
3. Part of antiretroviral therapy (ART) regimens.
False-negative test results in a laboratory test for HIV antibody may occur because of
a. heat inactivation of the serum before testing.
b. collection of the test sample before seroconversion.
c. interference by autoantibodies.
d. recent exposure to certain vaccines.
b. collection of the test sample before seroconversion.
False-negative HIV antibody test results can occur due to:
Timing Issues
1. Window period: Sampling before seroconversion (average 3-4 weeks, up to 3 months).
2. Early infection: Antibody levels may be undetectable.
Technical Factors
1. Insufficient sensitivity: Test limitations.
2. Sample handling errors: Improper storage, handling or transportation.
Biological Factors
1. Immunosuppression: Weakened immune response.
2. Coinfections: Certain infections (e.g., tuberculosis) affecting antibody production.
Rare Causes
1. Autoantibodies: Interfering with assay.
2. Vaccine interference: Uncommon.
To minimize false-negatives:
1. Repeat testing after 3-6 months.
2. Use combination assays (antibody/antigen).
3. Consider viral load (PCR) testing.
Which of the following combinations of bands would represent a positive Western blot for HIV antibody?
a. p24 and p55
b. p24 and p31
c. gp41 and gp120
d. p31 and p55
c. gp41 and gp120.
A positive Western blot for HIV antibody typically requires:
Required Bands
1. gp41 (envelope protein)
2. gp120 (envelope protein)
Optional Supporting Bands
1. p24 (core protein)
2. p31 (core protein)
Interpretation
1. Two or more specific HIV protein bands (gp41, gp120, p24, p31) confirm positivity.
2. Single-band presence or non-specific reactivity requires re-testing.
Western Blot Criteria
1. CDC: Two or more specific bands.
2. WHO: At least two bands (gp41, gp120, or p24).
The fourth-generation combination immunoassays for HIV detect
a. HIV-1 and HIV-2 antigens.
b. HIV-1 and HIV-2 antibodies.
c. p24 antigen.
d. HIV-1 antibodies, HIV-2 antibodies, and p24 antigen.
d. HIV-1 antibodies, HIV-2 antibodies, and p24 antigen.
Fourth-generation combination immunoassays (CIAs) detect:
1. HIV-1 antibodies (IgM/IgG)
2. HIV-2 antibodies (IgM/IgG)
3. p24 antigen (HIV-1)
These combination assays:
1. Improve sensitivity and specificity.
2. Reduce window period (average 14-24 days).
3. Enhance detection of acute infection.
Components:
1. Enzyme-linked immunosorbent assay (ELISA)
2. Chemiluminescent immunoassay (CLIA)
3. Immunochromatographic tests
The conjugate used in fourth-generation immunoassays for HIV consists of labeled
a. anti-human immunoglobulin.
b. HIV-1- and HIV-2-specific antibodies.
c. HIV-1- and HIV-2-specific antigens.
d. HIV-1- and HIV-2-specific antigens plus antibody to p24.
d. HIV-1- and HIV-2-specific antigens plus antibody to p24.
Fourth-generation HIV assays combine:
1. HIV-1/HIV-2 antigens
2. Anti-p24 antibody
Enabling simultaneous detection:
1. HIV-1/HIV-2 antibodies
2. p24 antigen
Improving sensitivity, specificity and reducing window period.
The characteristic laboratory finding in HIV infection is decreased
a. numbers of CD4 T cells.
b. numbers of CD8 T cells.
c. numbers of CD20 B cells.
d. immunoglobulins.
a. numbers of CD4 T cells.
HIV infection’s hallmark laboratory finding is:
Decreased CD4+ T-cell count
1. CD4+ T-cell depletion: Progressive decline in CD4+ T-cell numbers and percentage.
2. CD4/CD8 ratio reversal: Normal ratio (1:2) reverses due to decreased CD4+ and increased CD8+ T cells.
Other laboratory findings:
1. Increased viral load (HIV RNA)
2. Decreased lymphocyte count
3. Elevated liver enzymes
4. Thrombocytopenia (low platelet count)
Monitoring CD4+ T-cell count and viral load helps assess:
1. Disease progression
2. Treatment efficacy
3. Immune system recovery
Which of the following tests is currently recommended by the CDC to confirm a positive screening test result for HIV infection?
a. Rapid test for HIV-1 and HIV-2 antibodies
b. Western blot
c. Molecular testing for HIV RNA
d. HIV viral culture
a. Rapid test for HIV-1 and HIV-2 antibodies
The CDC guidelines replaced the Western blot with a rapid HIV-1/HIV-2 antibody test as the standard method for confirming positive screening results. Rapid tests are more suitable for confirmation because they can be performed more quickly, detect infection earlier, reduce the incidence of indeterminate results, and detect HIV-1 and HIV-2 infections simultaneously. However, HIV-1 Western blot testing still available in some reference laboratories and may be used as a confirmatory method in special situations, such as the testing of dried blood or urine or of samples that have indeterminate antibody screening results and test negative for HIV-1 RNA. (Stevens 5th Edition)
Which of the following tests would give the least reliable results in a 2-month-old infant?
a. CD4 T-cell count
b. ELISA for HIV antibody
c. PCR for HIV proviral DNA
d. p24 antigen
b. ELISA for HIV antibody.
In infants <18 months, maternal HIV antibodies can cause:
False-Positive Results
1. ELISA (HIV antibody test)
2. Rapid tests
Preferred Tests for Infants <18 months
1. PCR for HIV proviral DNA (c)
2. HIV viral culture
3. p24 antigen test (d)
Why CD4 T-cell count (a) is unreliable
1. Variability in normal ranges
2. Immature immune system
Which of the following measurements is/are routinely used to monitor patients with HIV infection who are undergoing antiretroviral therapy?
a. HIV antibody titer
b. p24 antigen levels
c. CD4 T-cell and CD8 T-cell counts
d. CD4 T-cell count and HIV RNA copy number
d. CD4 T-cell count and HIV RNA copy number
These measurements monitor:
CD4 T-cell Count
1. Immune system recovery
2. Treatment efficacy
3. Opportunistic infection risk
HIV RNA Copy Number (Viral Load)
1. Viral replication
2. Treatment response
3. Resistance development
4. Disease progression
Less commonly used:
b. p24 antigen levels (acute infection/diagnosis)
Not routinely used:
a. HIV antibody titer (diagnosis, not monitoring
c. CD8 T-cell counts (c) provide limited clinical utility.
